The proposed experiments are designed to elucidate the mechanisms whereby iodide and other related monovalent anions are actively transported across the basal and apical cell membranes of the thyroid gland and also the mechanisms by which this anion transport system is regulated by thyrotropin. Multiple approaches will be used to study these mechanisms. These involve: (1) compartmentation measurements of the thyroid; (2) kinetic studies with radioactive tracers of iodide, bicarbonate, and chloride uptake into whole thyroid glands and into luminal fluid, (3) histometric measurements of follicle, cell and luminal size, (4) electrolyte and acid-base measurements, (5) assay of the activities of various enzymes (carbonic anhydrase, and HCO3- and Na+, K+ ATPases) postulated to be involved in the thyroidal anion transport system, and (6) studies with H+, K+ and Cl-ion-selective and 3M KC1 microelectrodfes to assess the potentials across the apical and basal cell membranes, and the K+ and CT activities and pH of cellular and luminal fluids of the thyroid. Four different species will be used because their thyroids range from a high cellular to luminal volume ratio (mice and rats) to a very low ratio (guinea pigs and turtles), have different abilities to transport iodide, and the follicles vary in size from small to very large ( greater than 250 Mum). These experiments are designed to test the hypothesis that in addition to transport of iodide inward, the thyroid transports bicarbonate in the same direction, and chloride in the opposite direction, and that Na+, K+ ATPase, HCO3-ATPase and carbonic anhydrase are the transport enzymes involved. Thyrotropin is postulated to regulate iodide transport by an action on these enzymes, directly and/or indirectly.